• 사상체질의학회지
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• 제9권2호
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• pp.203-225
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• 1997

Jihwangbakhotang(地黃白虎楊) is made by Li Je Ma, the creator of the Four Constitutional Medicine. Single and 13 weeks oral repeated dose toxicity studies were conducted in Sprague Dawley rats of both sexes to elucidate the potential acute and subchronic toxicity of JBT extract and reversibility of any effects. In the single dose study, JBT extract was administered orally to rats with the dose of 2 g/kg and 8 g/kg. In the long term administration of 13 weeks, the JBT extract of 125 mg/kg/day, 500 mg/kg/day, 2000 mg/kg/day was administered to rats. The change of blood weight, urine volume, electrolyte in urine, hematological change, the change of blood chemistry, autopsy finding, and histological observation were researched, the results were as follows; 1. The lethal dose of JBT extract seems to be over 10 g/kg, the single administration of JBT extract 8 g/kg showed no toxical signs except little increase of urine volume. 2. The change of body weight had the trend of decrease in the group of, but has no significance, and also the consumption of food and water had no changes. 3. The hematological changes induced by the 13 weeks administration of JBT extract showed the significance in the item of Hb, MCH, MCV, WBC in the group of 125 mg/kg/day. 4. In the test of blood chemistry, total cholesterol showed little decrease and A/G ratio showed little increase, but the change was not clear, and the standard error was large. So the result was obtained insignificantly and the toxicity of JBT extract was not observed. 5. In the male group after recovery period, the level of cholesterol and triglyceride decreased slightly, but the result was not significant. 6. In the urine test, the little change of electrolyte was appeared, but it seemed not to be the result induced by the toxicity of JBT extract. 7. In each group of male and female rats, the weight change of organ and the serum histological changes was observed, but the result did not showed the dose dependent toxicity. So the toxicity of JBT extract was not regarded. In the conclusion, the toxicity of JBT extract was not observed in the single dose treatment and long term repetitive administration of JBT extract.

• Preventive Nutrition and Food Science
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• 제11권2호
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• 대한예방한의학회지
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• 제18권2호
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• pp.89-100
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• 2014

Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of GJD treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after co-administration with GJD as compared with sorafenib single treated rats. Accordingly, the $AUC_{0-t}$ (47.20%) of sorafenib was significantly increased but $t_{1/2}$ (-30.63%) and $MRT_{inf}$ (-34.11%) in co-administered rats were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability of sorafenib through increase of the absorption, when they co-administered within 5min. Conclusion : Based on the results, co-administration of GJD increased the oral bioavailability of sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the $T_{max}$ of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.

• 한방재활의학과학회지
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• 제25권3호
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• pp.1-9
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• 2015

Objectives To evaluate Shinbaro Pharmacopuncture safety through analysis of potential single-dose intramuscular toxicity of Sinbaro Pharmacopucture in SD rats and Beagle dogs. Methods Single-dose intramuscular toxicity of Shinbaro Pharmacopuncture was assessed in accordance with Korea Food and Drug Administration Guidelines for toxicity testing of Medicinal Products. The SD rats were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 0, 4.6, 9.2, and 18.5 mg/kg, respectively. The Beagle dogs were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 2.3, and 4.6 mg/kg, respectively, and after 3 days, the procedure was repeated a second time at doses of 0.6, and 1.2 mg/kg, respectively, for toxicity testing. Mortality, change in body weight, and necropsy findings were examined for the study period. Results There were no mortalities, general symptoms, or body weight changes in the SD rats. While pyelectasis of the left kidney was observed in a male rat in the 4.6 mg/kg administration group, natural occurrence is common, and does not appear to be related with the test substance. No mortalities were observed in the Beagle dogs. In assessment of general symptoms, a female dog in the 9.2 mg/kg group displayed body weight decrease due to leftover food, but the change in body weight was within the normal range seen at 6~7 months, and the necropsy findings were not significant. The toxicity of the test substance appears to be minimal. Conclusions The results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethaldose (ALD) value in single intramuscular administration of Shinbaro Pharmacopuncture in SD rats and Beagle dogs are higher than 18.5 mg/kg.

• 한국식품과학회지
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• 제46권2호
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• pp.249-255
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• 2014

본 연구에서는 사용된 가시오가피 영지버섯 발효물과 가시오가피 상황버섯 발효물에 대한 열수추출물을 최고 2 g/kg의 농도로 단회 투여한 SD-rats에 체중 변화, 임상증상 등에서 어떠한 독성도 관찰할 수 없었으며, 1 g/kg 이하의 농도로 4주간 반복 투여한 SD-rats에서도 체중변화, 임상증상, 장기 무게, 혈액학적 성상, 혈액생화학적 성상 등에서 어떠한 독성과 비정상적인 소견을 관찰할 수 없었다. 따라서, 본 연구의 결과로 볼 때 가시오가피 영지버섯 발효물 열수추출물(FM-5111)과 가시오가피 상황버섯 발효물 열수추출물(FM-5131)은 본 연구에서 사용한 농도 내에서의 안전성을 확인할 수 있었다. 황 함유 아미노산의 결핍은 여러 가지 간질환 등의 증상을 야기한다(27). 또한, Choi와 Ahn(28)은 오가피 부위별 50% (v/v) 메탄올 추출액의 전자공여능은 줄기 추출물에서 90.21%, 뿌리 추출물에서 85.71%로 높은 활성을 보고하여 오가피의 항산화능을 규명하였다. 따라서, 본 연구에 사용된 시료 또한 항산화능과 같은 기능성을 가질것으로 사료되며, 추가 연구로 아미노산 분석을 통해 황 함유 아미노산의 함량 변화를 분석하고 간 기능 개선 효능을 평가하여 안전성이 확보된 기능성 식품소재 개발 연구를 진행할 계획이다.

• 약학회지
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• 제43권6호
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• pp.729-735
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• 1999

Scopolia rhizome is mistaken as an atractylodes rhizome because of their similarities in shape. That is why atractylodes rhizome imported from China sometimes contain scopolia rhizome, which is very toxic. 8 persons were intoxicated atractylodes after taking imported atractylodes rhizome which is tainted. In kampo medicine prepared with such imported atractylodes rhizome, the level of tropane alkaloids ranged from 1.12∼4.34 mg/dose. In this study, we tried to investigate the tissue distribution of scopolia rhizome in rats. The extracts of scopolia was administered orally to rats (a single dose of 10mg/kg, 20mg/kg and 7 days repeated dose of 10mg/kg). Their blood was collected at 0.5, 1, 2, 4, 6 hrs, and liver, kidney, lung and spleen were collected after 6 hrs. The tissue homogenate was applied to solid phase extraction column for the determination of tropane alkaloids. After the oral administration of 20mg/kg scopolia extracts, l-hyoscyamine was detected in rat blood to 2 hrs after dosing. The concentration of tropane alkaloids was the highest in liver followed by lung, kidney and spleen. However, lung, kidney and spleen were similar in amount.

• Clinical and Experimental Pediatrics
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• 제50권6호
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• pp.531-535
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• 2007

목 적 : 인도메타신 투여는 미숙아 동맥관개존의 치료로 약 80-90%에서 효과를 보이며 일부는 반복 투여나 수술적 치료를 필요로 한다. 본 연구는 인도메타신 치료 효과에 영향을 미칠 수 있는 요인들을 분석하여 치료 효과를 관찰함으로써 조기에 인도메타신 재 투여나 수술적 치료를 고려해야 할 경우를 예측하는데 도움이 되는 인자를 알아보고자 시행되었다. 방 법 : 2002년 9월부터 2006년 4월까지 경희 의료원과 노원 을지병원 신생아 중환자실에 입원한 미숙아 중 동맥관개존을 진단받고 일차적으로 인도메타신 주사를 투여 받은 환아 29명을 대상으로 하였다. 이중 1 cycle 투여로 치료된 경우를 단일 투여 군으로, 약물을 재 투여하였거나 재 투여 후 수술적 치료를 받은 경우를 재 투여 군으로 하였으며 인도메타신 치료 효과에 영향을 줄 수 있는 인자들에 관하여 후향적으로 비교, 조사하였다. 결 과 : 단일 투여 군은 전체 29명 중 19명(65.5%)였고 재 투여군 중 수술적 치료 없이 인도메타신의 재 투여로 치료된 환아는 29명 중 5명(17.2%), 재 투여 후 재발하여 수술 받은 환아는 29명 중 5명(17.2%)이였다. 재 투여 군에서는 동맥관개존의 크기가 유의하게 더 컸으며($3.66{\pm}0.8mm$ vs $2.55{\pm}0.8mm$, P<0.01), 또한 인도메타신의 첫 투여 시 평균 연령은 재 투여 군에서 통계적으로 유의하게 높았다(19.7일 vs 12.5일, P<0.05). 재태 연령과 출생 체중은 의미 있는 차이는 없었다. 그밖에 기관지 폐 이형성증, 괴사성 장염, 패혈증, 뇌실 내 출혈 등과 같은 예후에도 양군간의 의미 있는 차이가 없었다. 결 론 : 동맥관개존의 크기가 3.5 mm 이상인 경우, 인도메타신 투여시기가 생후 7일 이상으로 늦은 경우에 적극적인 인도메타신의 재 투여나 수술적 치료를 고려해야 할 것으로 생각되며 향후 보다 많은 환자 군을 대상으로 하는 연구가 필요할 것으로 생각된다.

• Journal of Ginseng Research
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• 제19권2호
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• pp.101-107
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• 1995

The present study was undertaken to examine the effects of ginseng saponins [ginseng total saponin (GTS), protopanaxadiol saponin (PD) and protopanaxatriol saponin (PT)] on the hyperactivity, reverse tolerance and dopamine receptor super-sensitivity induced by cocaine. A single treatment with cocaine produced hyperactivity. Repeated administration of cocaine developed reverse tolerance and dopamine receptor super-sensitivity was also developed in reverse tolerant mice which had received the same cocaine. The hyperactivity and the developments of reverse tolerance and dopamine receptor super-sensitivity by cocaine were inhibited by ginseng saponins. From these results, it is proposed that ginseng saponins may be useful for the prevention and therapy of the adverse actions of cocaine. In addition, the rank order of inhibitory potential was observed as PT>GTS>PD. Key words Cocaine, hyperactivity, reverse tolerance, dopamine receptor super-sensitivity, ginseng saponins.

• Toxicological Research
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• 제13권3호
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• pp.237-245
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• 1997

As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

• Asia Marketing Journal
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• 제15권3호
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• pp.159-172
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• 2013

In the present study, we apply the multiple cue probability learning (MCPL) paradigm to examine consumer learning from feedback in repeated trials. This paradigm is useful in investigating consumer learning, especially learning the relationships between the overall quality and attributes. With this paradigm, we can analyze what people learn from repeated trials by using the lens model, i.e., whether it is knowledge or consistency. In addition to introducing this paradigm, we aim to demonstrate that knowledge people gain from repeated trials with feedback is robust enough to weaken one of the most often examined contextual effects, the asymmetric dominance effect. The experiment consists of learning session and a choice task and stimuli are sport rafting boats with motor engines. During the learning session, the participants are shown an option with three attributes and are asked to evaluate its overall quality and type in a number between 0 and 100. Then an expert's evaluation, a number between 0 and 100, is provided as feedback. This trial is repeated fifteen times with different sets of attributes, which comprises one learning session. Depending on the conditions, the participants do one (low) or three (high) learning sessions or do not go through any learning session (no learning). After learning session, the participants then are provided with either a core or an extended choice set to make a choice to examine if learning from feedback would weaken the asymmetric dominance effect. The experiment uses a between-subjects experimental design (2 × 3; core set vs. extended set; no vs. low vs. high learning). The results show that the participants evaluate the overall qualities more accurately with learning. They learn the true trade-off rule between attributes (increase in knowledge) and become more consistent in their evaluations. Regarding the choice task, there is a significant decrease in the percentage of choosing the target option in the extended sets with learning, which clearly demonstrates that learning decreases the magnitude of the asymmetric dominance effect. However, these results are significant only when no learning condition is compared either to low or high learning condition. There is no significant result between low and high learning conditions, which may be due to fatigue or reflect the characteristics of learning curve. The present study introduces the MCPL paradigm in examining consumer learning and demonstrates that learning from feedback increases both knowledge and consistency and weakens the asymmetric dominance effect. The latter result may suggest that the previous demonstrations of the asymmetric dominance effect are somewhat exaggerated. In a single choice setting, people do not have enough information or experience about the stimuli, which may lead them to depend mostly on the contextual structure among options. In the future, more realistic stimuli and real experts' judgments can be used to increase the external validity of study results. In addition, consumers often learn through repeated choices in real consumer settings. Therefore, what consumers learn from feedback in repeated choices would be an interesting topic to investigate.